Search Results (2,730)

Acquired resistance to targeted therapies is inevitable in EGFR-mutant non-small cell lung cancer (NSCLC), yet the principles governing its emergence in vivo remain incompletely understood. In particular, how lesion-level response patterns vary across distinct EGFR allele contexts during therapy has not been systematically examined at single-lesion resolution. Here, we establish a longitudinal in vivo imaging platform enabling single-lesion resolution tracking of tumor behavior during therapy in genetically engineered mouse models representing clinically relevant EGFR alleles. Using high-resolution micro-computed tomography (micro-CT) and three-dimensional reconstruction, we monitor tumor growth, therapeutic response, and resistance during osimertinib treatment. EGFR genotype is associated with distinct patterns of tumor growth, response kinetics, and resistance timing. Therapeutic response is spatially heterogeneous, with coexisting lesions undergoing complete regression, persistence, or progression within the same lung. During treatment, spatially distinct lesion-level behaviors included persistent growth during therapy and initial regression followed by regrowth. These findings demonstrate the utility of longitudinal micro-CT imaging to investigate allele-associated differences in treatment response and resistance timing at single-lesion resolution in vivo. Full article

Immune checkpoint blockade (ICB) has transformed cancer therapy, but clinical responses remain heterogeneous across tumor types and patient populations. Cancer-associated fibroblasts (CAFs) are key stromal components of the tumor microenvironment and can contribute to immunotherapy resistance through immune exclusion, extracellular matrix remodeling, chemokine signaling, and interactions with suppressive immune cells. Although CAF-directed strategies are under active investigation, their clinical translation is limited by marked CAF heterogeneity and the lack of scalable biomarkers for patient stratification. Computational pathology based on hematoxylin and eosin (H&E) whole-slide images (WSIs) provides a potential approach for extracting stromal and spatial features from routine histology, although digitized WSIs and the infrastructure required for large-scale AI analysis are not universally available. In this review, we synthesize current evidence on CAF classification, CAF-mediated immunotherapy resistance, H&E-based computational pathology, and emerging histology-based biomarker models. We further propose a conceptual roadmap for developing CAF-aware H&E spatial signatures with potential relevance to future immunotherapy stratification. Current evidence supports the biological rationale and computational feasibility of this approach, whereas its clinical utility remains to be established through rigorous external validation and prospective clinical evaluation. Full article

Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality, and internal radionuclide therapy is an important locoregional option for unresectable disease. This review summarizes the current landscape of transarterial radionuclide therapy for HCC and, as a translational perspective, considers how the carrier, radionuclide, and dosimetry concepts established in HCC may extend to secondary liver tumors (liver metastases). It begins with established transarterial radioembolization (TARE/selective internal radiation therapy, SIRT) using yttrium-90 (⁹⁰Y) microspheres and the shift toward personalized dosimetry and combination with systemic and immune-based therapies. It then examines alternative radionuclides and carrier systems—including holmium-166 (¹⁶⁶Ho) microspheres, iodine-131 (¹³¹I) lipiodol, rhenium-188 (¹⁸⁸Re) lipiodol, and lutetium-177 emulsified in lipiodol (¹⁷⁷Lu-lipiodol)—from the standpoint of their physical properties, radiochemistry, theranostic potential, and preclinical and clinical evidence. Particular attention is given to ¹⁷⁷Lu-based approaches, including their favorable beta energy, the concurrent imageable gamma emission that enables single-photon emission computed tomography (SPECT)-based dosimetry, and the potential to address post-embolization hypoxia-related radioresistance, while noting that the clinical evidence for ¹⁷⁷Lu-lipiodol remains preclinical. The application of these platforms to colorectal and neuroendocrine liver metastases is then outlined. Finally, regulatory, radiation safety, and waste management considerations and the principal challenges to clinical translation are discussed. Full article

Liver transplantation (LT) has evolved from a contraindicated procedure for malignancy into an established oncologic therapy for selected primary and secondary hepatic cancers. Advances in tumor biology, molecular profiling, immunotherapy, and peri-transplant management have expanded transplant indications beyond hepatocellular carcinoma (HCC) to include perihilar cholangiocarcinoma, intrahepatic cholangiocarcinoma, colorectal liver metastasis (CRLM), neuroendocrine liver metastasis (NELM), and rare hepatic malignancies. The 2024 TransMet randomized controlled trial, demonstrating a 5-year overall survival (OS) of 73% with LT plus chemotherapy versus 9% with chemotherapy alone for unresectable CRLM, established the first Level 1 evidence supporting transplantation as a curative oncologic intervention in metastatic disease. These advances necessitate a modern framework for clinical trial design and research prioritization in transplant oncology. This manuscript proposes a comprehensive framework for future transplant oncology trials addressing endpoint selection, biomarker-driven patient selection, trial methodology, immunosuppression optimization, surveillance strategies, and ethical organ allocation. OS and transplant benefit are emphasized as the preferred primary endpoints for CRLM and NELM, whereas recurrence-free survival is recognized as retaining distinct clinical and prognostic value in HCC, underscoring that endpoint selection should be disease-specific rather than universally standardized. Emerging biomarkers—including circulating tumor DNA, AFP dynamics, and molecular and functional imaging profiling—are stratified into established, prospectively validated, and investigational categories to clarify their current clinical applicability. Randomized controlled trials, adaptive platform and enrichment designs, biomarker-stratified randomization, registry-based trials, and prospective registries are presented as complementary strategies tailored to disease prevalence and feasibility, alongside explicit consideration of how graft source—particularly the predominance of living donor liver transplantation in Asia versus deceased donor systems elsewhere—shapes trial design and interpretation. The manuscript further examines tumor biology-based immunosuppression, immune checkpoint inhibitor integration, and management of post-transplant recurrence. A precision medicine vision is proposed in which transplant candidacy is determined by biologic behavior and molecular signatures rather than morphology alone, with proposed trial frameworks offering an actionable research agenda for the next decade of transplant oncology. Full article

Liver tumor segmentation is a significant task in clinical imaging that involves detecting liver tumors and distinguishing them from the surrounding liver tissue in CT scans. Precision segmentation performs important roles in the initial detection of liver cancer, treatment planning, and monitoring disease development, which also supports doctors, facilitating surgeries and radiation therapy more efficiently. Meanwhile, clinical imaging and segmentation algorithms have been enhanced over the years. The currently prevailing state-of-the-art methods still face multiple difficulties, though, in obtaining precision and reliability in their outcomes. Tumors with irregular shapes, variable sizes, and densities similar to those of surrounding tissues often lead to segmentation inaccuracies and potential misdiagnoses. In this work, we tackle these challenges by developing an advanced process for precise liver tumor segmentation by utilizing CT images from the LiTS dataset. The proposed DTARNU-Net was developed, trained, validated, and evaluated exclusively using the Liver Tumor Segmentation (LiTS) benchmark dataset. No experiments were conducted on the 3D-IRCADbI dataset in this study. All quantitative and qualitative results presented in the manuscript correspond to the LiTS dataset. The LiTS dataset contains contrast-enhanced abdominal CT scans with expert-annotated liver and tumor masks. The proposed model was evaluated using patient-level training, validation, and testing partitions (9:2:2 ratio), and all experiments were independently repeated five times. Statistical significance was assessed using paired Student’s t-test (p < 0.05), and the results confirmed that the performance improvements over competing methods are statistically significant. We introduce a novel three-level pre-processing approach that significantly enhances image quality through histogram equalization, noise removal, smoothing, and sharpening. Our approach is embodied in the Dense Tiered Attention Residual Nested U-Net (DTARNU-Net), a sophisticated model combining the strengths of a Siamese network and a nested U-Net architecture. This model incorporates the ACON-ReLU residual convolution block (A-R), which improves recognition accuracy in regions with subtle changes, reducing missed detection. The presented method enhances trait collaboration and spatial data by utilizing the Brownian Motion-based Butterfly Optimization Algorithm (BM-BOA). This algorithm efficiently integrates low-level trait details with high-level semantic data. The Dense Tiered Attention Residual Module (DTSRM) additionally improves these traits to obtain more precise segmentation. The model achieved segmentation robustness of 96.78% for liver segmentation and 97.00% for liver tumor segmentation on the LiTS dataset. These outcomes indicate that the presented method performs better than the prevailing state-of-the-art methods and has the capability to help computer-assisted detection and treatment by furnishing more precise and reliable liver tumor segmentation. Full article

With immune checkpoint inhibitors becoming the mainstay of systemic therapy in both metastatic and early-stage settings across many cancer types, the management of immune-related adverse events has emerged as a central priority of modern oncological supportive care. These toxicities can substantially impair the quality of life of cancer patients, including those who achieve long-term survival. Consequently, there is a pressing need to develop reliable predictive biomarkers to better tailor immune checkpoint inhibitor treatment and optimize patient selection. This review summarizes several of the most promising predictive biomarkers currently under investigation, including genetic factors; peripheral blood parameters and their ratios; autoantibodies; cytokines and chemokines; cytomegalovirus serostatus; gut microbiome characteristics; body composition metrics; molecular imaging features; and tumour- and patient-related factors such as cancer type, gender, and physical activity. Because single biomarkers have limited predictive value, multi-omics prediction models and composite immune-cell scores are increasingly demonstrating greater potential. However, none of these candidate biomarkers have yet undergone sufficient validation to support their incorporation into routine clinical practice. Full article

Background: Sarcopenia, systemic inflammation, and malnutrition are established poor prognostic factors in renal cell carcinoma (RCC). This study investigated the utility of a novel preoperative score combining psoas muscle density (PMD)—an imaging-based indicator of muscle quality—and the albumin–bilirubin (ALBI) grade—a blood-based biomarker of liver reserve and systemic nutritional status—for predicting disease-free survival (DFS) and overall survival (OS) in patients undergoing curative surgery for RCC. Methods: This retrospective observational study included 274 patients with non-metastatic RCC treated with radical or partial nephrectomy. Preoperative computed tomography was utilized to measure PMD, defining “low PMD” as a value below the sex-specific median (males: 47.75 Hounsfield Units [HU]; females: 46.25 HU). “Worsened ALBI” was defined as an ALBI grade ≥ 2. Patients were stratified into three risk categories: Score 0 (both normal, n = 122), Score 1 (either abnormal, n = 114), and Score 2 (both abnormal, n = 38). Results: Kaplan–Meier analysis revealed a highly significant, stepwise decline in both DFS and OS as the risk score increased (log–rank p < 0.001 and p = 0.004, respectively). Multivariate Cox regression identified the combined risk score as a robust, independent prognostic factor for DFS (Score 1: HR 1.93, 95% CI 1.11–3.37, p = 0.020; Score 2: HR 3.58, 95% CI 1.82–7.02, p < 0.001). Furthermore, after adjusting for age and comorbidities, the score remained an independent predictor of poor OS (Score 1: HR 2.35, 95% CI 1.08–5.13, p = 0.032; Score 2: HR 3.01, 95% CI 1.16–7.82, p = 0.024). The combined model synergistically enhanced risk stratification accuracy compared to evaluating either factor independently. Conclusions: The concurrent presence of preoperative low PMD and a worsened ALBI grade is a powerful, independent predictor of poor prognosis in localized RCC. Derived solely from routine preoperative imaging and laboratory tests, this straightforward scoring system effectively captures the structural and immunometabolic dimensions of cancer cachexia and host vulnerability. This tool can significantly aid in personalizing postoperative surveillance strategies and identifying high-risk patients who may warrant closer postoperative surveillance or who might be considered as high-risk candidates for adjuvant therapy discussions. Full article

Background: Patient-specific targeted radionuclide therapy (TRT) requires consideration not only of administered activity but also of the spatial distribution of radiopharmaceutical uptake and radionuclide-specific energy deposition. This study developed a voxel-based computational workplan to compare ¹⁷⁷Lu, ¹⁶¹Tb and ⁹⁰Y, together with hybrid radionuclide models, using patient-specific PSMA PET-derived tumour activity distributions. Methods: PSMA PET/CT data from 20 patients with prostate cancer, comprising 10 ¹⁸F-PSMA and 10 ⁶⁸Ga-PSMA examinations, were processed to obtain 2285 quality-filtered lesions. Radionuclide-specific dose-point kernels (DPKs) were generated in water using OpenGATE and applied to voxel-wise lesion activity distributions to reconstruct absorbed-dose maps. Kernel characteristics were evaluated using radial energy-containment metrics, and ¹⁷⁷Lu, representing ¹⁶¹Tb simulations, was subjected to grid-convergence testing and external comparison with a published DPK. Lesion dosimetry was assessed using Dmean, D90, D95, equivalent uniform dose (EUD) and tumour control probability (TCP), with uncertainty quantified using patient-cluster bootstrap confidence intervals. Kinetic sensitivity and diagnostic tracer subgroup analyses were additionally performed. Results: The study showed that ¹⁶¹Tb produced the highest median lesion-level Dmean, D90, D95 and EUD at 182.79, 136.28, 132.07 and 148.53 Gy, respectively, with a median TCP of 0.981. Corresponding values for ¹⁷⁷Lu were 141.33, 105.42, 102.10 and 114.78 Gy (TCP 0.930), while ⁹⁰Y produced lower local dose metrics but the broadest radial dose distribution, consistent with its longer-range β-particle crossfire. ¹⁶¹Tb remained the highest-ranking radionuclide across the investigated kinetic cases and within both diagnostic tracer subgroups. Hybrid ¹⁶¹Tb/⁹⁰Y kernels provided a controllable compromise between localised energy deposition and extended crossfire; a 70:30 model increased central dose localisation while retaining an R90 and R95 of 6 and 7 mm, respectively. Grid-convergence and published-DPK comparisons supported the numerical adequacy of the kernel methodology. Radionuclide emission characteristics substantially influence the transformation of heterogeneous tumour uptake into spatial absorbed-dose distributions. Within this model, ¹⁶¹Tb provided the strongest overall lesion-level dosimetric performance, whereas the extended range of ⁹⁰Y may offer complementary crossfire for selected bulky or heterogeneous lesions. Conclusions: The findings support phenotype-informed radionuclide comparison and provide a computational basis for investigating hybrid strategies. However, the absolute dose estimates and proposed radionuclide combinations remain model-based and require validation using serial therapeutic imaging, heterogeneous patient-specific dosimetry and normal-organ dose constraints before clinical translation. Full article

Background/Objectives: Breast cancer is the most frequently diagnosed cancer among women worldwide and a leading cause of cancer-related death. Despite the use of bisphosphonates, RANKL inhibitors, chemotherapy, and available endocrine therapies, the five-year survival rate for patients with bone metastases remains approximately 20–30%, underscoring the urgent need for novel, metastasis-specific therapeutic strategies. Recent studies demonstrated that miR-10b can serve as an attractive therapeutic target for the treatment of metastatic breast cancer, particularly in the context of bone metastasis. This study aimed to test antimir-10b therapeutics in a mouse model of breast cancer bone metastasis. Methods: We utilized a previously developed dextran-coated iron oxide nanoparticle-based platform for delivery of antisense anti-miR-10b oligonucleotides to bone metastases. The magnetic properties of the nanoparticles allowed for in vivo imaging of therapeutic delivery to metastatic tumors. Results: We showed the delivery of the therapeutics in the bone colonization model by in vivo imaging as well as significant survival benefits in injected animals. There was a significant inhibition of miR-10b following treatment that resulted in significant upregulation of the downstream target HOXD10 in vitro and a similar trend in vivo. Repeated dosing of the therapeutics was well tolerated, and no systemic toxicity was observed, supporting the safety profile of this approach. Conclusions: Collectively, these studies demonstrated that targeting miR-10b using an image-guided anti-miR-10b nanotherapeutic represents a promising and translatable strategy for targeting breast cancer bone metastases. Full article

Background: Neoadjuvant systemic therapy (NST) enables tumor downsizing and increases the feasibility of breast-conserving surgery (BCS) in patients with early breast cancer (EBC). Reliable tumor localization after NST remains challenging, particularly in patients with a complete clinical response. If clips are not visible on ultrasound, stereotactic mammography-guided wire localization is required, which involves additional radiation exposure and may increase patient discomfort and procedural complexity. The 3D-shaped Tumark^® Vision clip may enable ultrasound-guided localization after NST. Methods: In this prospective multicenter registry study (NCT04468113), 324 patients with biopsy-proven EBC scheduled for NST and breast-conserving surgery were enrolled across 19 German centers. Clip placement was performed under ultrasound guidance prior to NST, and clip detectability was assessed at predefined time points during therapy (4–8, 9–12, and ≥13 weeks after treatment initiation). Detection rates, visualization, and preoperative localization methods were recorded. Non-detectable clips required stereotactic wire localization, whereas ultrasound-guided localization was performed for detectable clips. Results: The preoperative detection rate was 91.1%. Clip detectability was higher in patients with longer NST durations and partial response by imaging. Ultrasound-guided wire localization was feasible in 214 patients (83.9%); among these, 165 patients (64.7%) underwent localization without and 49 patients (19.2%) with post-procedural mammographic verification. Stereotactic localization was required in 41 patients (16.1%), primarily due to non-visualization of the clip on ultrasound. The accuracy of ultrasound for residual tumor assessment was moderate (72.0%), with a sensitivity of 70.7%, indicating limitations in its ability to reliably assess residual tumor extent as a standalone modality. Conclusions: The 3D nickel–titanium clip enables ultrasound-guided tumor localization after NST in the majority of patients with early breast cancer, although additional mammographic guidance remains necessary in a relevant proportion of cases. Full article

Mesoporous silica nanoparticles (MSNs) have emerged as versatile nanocarriers for biomedical applications because of their unique physicochemical properties, including high surface area, large pore volume, excellent drug-loading capacity, controllable biodegradation, and facile surface functionalization. These characteristics have enabled the development of advanced drug delivery systems with enhanced therapeutic efficacy, targeted delivery, improved bioavailability, and reduced systemic toxicity. Recent advances in MSN synthesis, physicochemical properties, surface engineering, and functionalization strategies have significantly improved their biological performance and therapeutic potential. In particular, integrating polymers, lipids, and liposomes with MSN platforms has enhanced colloidal stability, circulation time, cellular uptake, and target specificity, thereby facilitating efficient, stimuli-responsive drug delivery. This review highlights MSN-based drug delivery systems in cancer therapy, where multifunctional nanocarriers enable site-specific delivery, controlled drug release, enhanced tumor accumulation, and reduced off-target effects. The review discusses the expanding roles of MSNs in antimicrobial therapy, wound healing, tissue engineering, and regenerative medicine, emphasizing their ability to promote localized therapeutic delivery, immunomodulation, angiogenesis, and tissue regeneration. The review discusses the diagnostic and theragnostic capabilities of MSNs for disease imaging and monitoring. It also critically evaluates current challenges related to biocompatibility, biodegradation, toxicity, biological barriers, large-scale manufacturing, clinical translation, and regulatory considerations. This review provides a comprehensive overview of recent progress, current limitations, and future opportunities for MSN-based platforms in targeted drug delivery and advanced biomedical applications, supporting their continued advancement toward clinical translation and precision medicine. Full article

Differentiated thyroid carcinoma is a morphologic diagnosis, not a direct measure of preserved thyroid function. Although most papillary, follicular, and oncocytic thyroid carcinomas retain architectural or cytologic features of follicular-cell derivation, a clinically important subset loses the molecular machinery required for effective iodine transport, organification, and radioiodine therapy. This functional divergence is central to the biology of radioiodine-indifferent and radioiodine-refractory thyroid cancer. This review examines the role of oncogenic MAPK/ERK signaling as a principal regulator of thyroid lineage suppression and therapeutic failure. Aberrant activation of the RAF–MEK–ERK axis, most prominently through BRAF^V600E, RAS alterations, and receptor tyrosine kinase fusions, does more than promote proliferation. It reshapes follicular-cell identity by repressing thyroid-lineage transcriptional programs and silencing iodine-handling genes, including SLC5A5/NIS, TPO, TG, TSHR, SLC26A4, and related components of the iodine metabolic transcriptome. This repression is mediated through coordinated transcriptional, epigenetic, and post-transcriptional mechanisms involving lineage transcription factors such as PAX8, NKX2-1, and FOXE1; chromatin-modifying programs including histone deacetylation and PRC2/EZH2-associated repression; DNA methylation; and non-coding RNA networks. Importantly, ERK-driven functional dedifferentiation is not always a fixed terminal state. Preclinical models and early clinical trials demonstrate that pharmacologic inhibition of the MAPK pathway can restore iodine avidity in selected radioiodine-refractory tumors, creating the theranostic basis for redifferentiation therapy. Iodine-124 PET/CT and lesion-level dosimetry have shown that restored iodine uptake can be measured diagnostically and then exploited therapeutically with iodine-131. However, clinical translation remains limited by inter- and intratumoral heterogeneity, incomplete durability of response, adaptive pathway reactivation, persistent epigenetic repression, tumor microenvironmental influences, and the absence of standardized dosimetric thresholds. We propose that advanced follicular-cell-derived thyroid cancers should be understood along a functional differentiation continuum rather than through morphology alone. Within this framework, radioiodine refractoriness reflects not merely treatment failure, but a therapeutically interrogable state of lineage suppression. Refinement of redifferentiation therapy will require genotype-informed patient selection, functional imaging, standardized dosimetry, rational combination strategies, and prospective trials capable of distinguishing true restoration of radioiodine therapeutic efficacy from the antiproliferative effects of kinase inhibition alone. Full article

Background/Objectives: Circulating tumor-associated cells (CTACs) are rare among peripheral blood nucleated cells (PBNCs), creating a challenge for image-based multi-cancer detection. We evaluated a predefined CTAC-detection pipeline incorporating Attention U-Net segmentation, post-processing, cytological feature extraction, and Random Forest classification. Methods: Model suitability was explored in asymptomatic individuals and patients with advanced solid tumors. Clinical performance was assessed in a case–control cohort of therapy-naive stage I/II cancers, benign conditions, and asymptomatic individuals, followed by four prospective cohort evaluations performed within the same laboratory and imaging workflow: recurrent cancer with low radiological tumor burden, peri-operative solid tumors, suspected cancer, and asymptomatic screening. PBNCs were stained with EpCAM/Hoechst 33342 and imaged. Pathologists’ review established ground truth annotations. Results: The model had 90.68% sensitivity and 99.53% specificity in the exploratory study. In the case–control cohort, sensitivity was 88.65% in therapy-naive stage I/II cancers, while specificity was 78.95% in benign conditions and >99.9% in asymptomatic individuals. In the prospective cohorts, CTAC detection sensitivity was 91.96% in pretreated low tumor burden cases; CTACs were detected in 100% of pre-surgery specimens and 29.41% of post-surgery specimens; and in suspected cancer cases, the Positive Predictive Value (PPV) and Negative Predictive Value (NPV) were 96.34% and 32.35%, respectively. In the asymptomatic screening cohort, 44/7183 participants were CTAC-positive; 16 had confirmed Stage I/II cancer, 10 had no radiologically detectable disease at the available assessment, and 18 remained unresolved. The conservative lower-bound PPV was 36.36%, and the NPV was 99.97%; estimates remain provisional pending complete follow-up. Conclusions: The integrated Attention U-Net/feature-based classification pipeline demonstrated consistent CTAC detection across the evaluated cohorts and supports its potential clinical utility for cancer detection. Full article

Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment landscape of hematologic malignancies but has demonstrated limited efficacy in solid tumors, mainly due to the complex and immunosuppressive tumor microenvironment (TME). Among the strategies to overcome this challenge, targeting the tumor stroma rather than the tumor cells themselves has gained increasing interest. In this context, fibroblast activation protein alpha (FAP), a cell surface protease overexpressed by cancer-associated fibroblasts, represents a promising target. With the aim of remodeling the TME, enhancing immune infiltration, and suppressing tumor growth, numerous FAP-directed CAR T-cell therapies have been developed in the last decade, leading to the clinical translation of two candidates. To improve the flexibility and safety profile of CAR T-cell therapies, several groups have designed more controllable and modular approaches, including adapter CAR T-cell systems, which enable on-demand activation of effector cells through the administration of an adapter molecule. In parallel, the development of FAP-targeted radiotracers, particularly FAP inhibitors (FAPIs), has enabled high-contrast imaging of solid tumors and introduced attractive opportunities for radioligand therapy. The convergence of these advances has given rise to immunotheranostic strategies that integrate CAR T-cell immunotherapy and radioligand delivery within a unified framework. This review traces the evolution of FAP-directed CAR T-cell strategies, from conventional designs to adapter-based and theranostic platforms, and examines how modular adapters bring immunotherapy and radioligand delivery together within a single immunotheranostic framework, across preclinical and clinical settings. Full article

Background/Objectives: Total en bloc spondylectomy (TES) remains one of the most invasive and selectively used procedures in spine oncology. Its role has become more selective in the modern era of stereotactic body radiotherapy, separation surgery, targeted systemic therapy, immunotherapy, and multidisciplinary cancer care. This study evaluated long-term survival, imaging-defined systemic disease burden, operative morbidity, patient-reported outcomes, and frailty-related variables after TES in a rare single-center cohort, with the goal of identifying selection-relevant survival and treatment-burden signals rather than developing a validated decision algorithm. Methods: We performed a retrospective single-center cohort study of consecutive adults who underwent TES for spinal tumors between 2011 and 2022. Of the 36 screened patients, 30 had sufficient clinical and survival data for analysis; patients without reliable survival or last-contact data were not included. Contrast-enhanced CT and PET-CT were reviewed for extraspinal metastases, lymphadenopathy, pleural effusion, and soft-tissue extension. Survival was analyzed using Kaplan–Meier methods, log-rank testing, and exploratory univariate Cox regression. Patient-reported outcomes included the Oswestry Disability Index (ODI) and SF-36 when available; frailty was summarized with the modified frailty index-5 (mFI-5) when component data were present. Results: The cohort included 13 men and 17 women with a mean age of 54.8 ± 15.2 years. At final follow-up, 18 patients had died, and 12 were alive. Five-year overall survival was approximately 76% in the full cohort. Extraspinal metastases were present in 72.2% of deceased patients compared with 8.3% of survivors and showed the clearest exploratory association with increased mortality (HR 3.46, 95% CI 1.23–9.78; p = 0.019). Metastatic disease demonstrated inferior survival compared with primary bone or soft-tissue tumors. Perioperative blood loss and transfusion burden were substantial but were not associated with survival in univariate analysis. ODI and SF-36 data were available only in small subsets and were therefore interpreted as descriptive signals of treatment burden. Conclusions: TES remains relevant in modern spine oncology, but only as an increasingly selective intervention. In this rare cohort, systemic disease burden, particularly extraspinal metastases, was the clearest selection-relevant survival signal, while blood loss, transfusion requirements, complications, and limited patient-reported outcomes illustrated substantial treatment burden. These findings do not establish a validated selection algorithm but support a contemporary decision threshold that integrates tumor biology, systemic disease status, anticipated margins, physiologic reserve, operative morbidity, and patient goals. Full article